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MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation.

Yair Dorsett | Kevin M McBride | Mila Jankovic | Anna Gazumyan | To-Ha Thai | Davide F Robbiani | Michela Di Virgilio | Bernardo Reina San-Martin | Gordon Heidkamp | Tanja A Schwickert | Thomas Eisenreich | Klaus Rajewsky | Michel C Nussenzweig
Immunity | 2008

MicroRNAs (miRNAs) are small noncoding RNAs that regulate vast networks of genes that share miRNA target sequences. To examine the physiologic effects of an individual miRNA-mRNA interaction in vivo, we generated mice that carry a mutation in the putative microRNA-155 (miR-155) binding site in the 3'-untranslated region of activation-induced cytidine deaminase (AID), designated Aicda(155) mice. AID is required for immunoglobulin gene diversification in B lymphocytes, but it also promotes chromosomal translocations. Aicda(155) caused an increase in steady-state Aicda mRNA and protein amounts by increasing the half-life of the mRNA, resulting in a high degree of Myc-Igh translocations. A similar but more pronounced translocation phenotype was also found in miR-155-deficient mice. Our experiments indicate that miR-155 can act as a tumor suppressor by reducing potentially oncogenic translocations generated by AID.

Pubmed ID: 18455451

Research resources used in this publication

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI037526
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI037526-15
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI037526-06
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI037526-14
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI037526-09
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI037526-13
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI037526-12
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI037526-11
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI037526-08
  • Agency: NIAID NIH HHS, United States
    Id: AI06231
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI064345
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI037526-10
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI037526-07
  • Agency: NIAID NIH HHS, United States
    Id: AI064345

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